The filariae are thread-like parasitic nematodes (roundworms) that are transmitted by arthropod vectors. The adult worms inhabit specific tissues where they mate and produce microfilariae, the characteristic tiny, thread-like larvae.
The microfilariae infect vector arthropods, in which they mature to infective larvae. Diseases caused by filariae are a major health problem in many tropical and subtropical areas. Wuchereria bancrofti and Brugia malayi are filarial parasites that are the major causative agents of lymphatic filariasis. Currently, it is estimated that over 129 million people are infected with either of these organisms and over one billion live in at-risk areas. Since 2000, there has been an ongoing effort through the Global Program to Eliminate Lymphatic Filariasis to eradicate these infections. While this program is having a substantive impact on the prevalence of infection, its efficacy is limited by the need to repeatedly treat entire endemic populations for 6-10 years. The advent of new tools, such as vaccines or more effective anthelmintics, would be of great benefit toward these eradication efforts.
One of the principle obstacles in designing vaccines against such parasitic worms, however, is that previously exposed individuals frequently have IgE antibodies to surface and secreted worm antigens, putting them at risk for allergic reactions when re-exposed to these antigens. Since intestinal antigens of helminths may be “hidden” from the immune response during natural infection, yet accessible by antibodies after antigen administration, homogenates of such antigens have been proposed for use in vaccines. However, while the genomes of Wuchereria bancrofti and Brugia malayi, as well as the filarial genomes of the causative agents of loiasis and river blindness have been completed, the anatomic localization of proteins in these filarial worms is unknown. Moreover, the use of homogenates from helminth intestines has resulted in variable efficacy.
Other diseases known in the art, which are caused by filarial parasites, include heartworm disease. This disease is caused by the parasite Dirofilaria immitis. The physical presence of the heartworm parasite in the pulmonary artery and right ventricle of the canine heart, for example, and the resulting destruction of tissue, causes respiratory and circulatory problems which can be fatal under conditions of stress or vigorous exercise. The heartworm parasite has also been shown to be the cause of focal lung, liver, eye and cutaneous lesions in man. Currently, heartworm disease is treated by administering anti-parasitic agents to infected animals. Unfortunately, heartworm disease that has not been diagnosed in its early stages may be quite refractile to treatment.
Accordingly, there is a need in the art for immunogenic compositions, such as vaccines, which may be used to prevent or treat diseases caused by filarial worms including lymphatic filariasis, loiasis, river blindness and heartworm.